A Dual-Targeting Liposome Enhances Triple-Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation
Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.
基金：
National Natural Science Foundation of China [82204633]; China Postdoctoral Science Foundation [2021M700550]; Sichuan Science and Technology Program [2022NSFSC0634, 2023NSFSC1782]; Key Research and Development Program of Science and Technology Department of Sichuan Province [2023YFS0110]; Talent Research Promotion Plan of "Xinglin Scholar" Discipline in Chengdu University of Traditional Chinese Medicine [BSH2021024]
第一作者机构：[1]Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China
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推荐引用方式(GB/T 7714)：
Luo Kaipei,Yang Lu,Yan Chunmei,et al.A Dual-Targeting Liposome Enhances Triple-Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation[J].SMALL.2023,19(40):doi:10.1002/smll.202302834.
APA：
Luo, Kaipei,Yang, Lu,Yan, Chunmei,Zhao, Yuxin,Li, Qiuxia...&Li, Xiaofang.(2023).A Dual-Targeting Liposome Enhances Triple-Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation.SMALL,19,(40)
MLA：
Luo, Kaipei,et al."A Dual-Targeting Liposome Enhances Triple-Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation".SMALL 19..40(2023)
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